Evidence map›Paper›PMID 33731134›Full record

ArticleMalaria journal2021

Temporal evolution of sulfadoxine-pyrimethamine resistance genotypes and genetic diversity in response to a decade of increased interventions against Plasmodium falciparum in northern Ghana.

Lucas N Amenga-Etego, Victor Asoala, Godfred Agongo, Christopher Jacob, Sonia Goncalves, Gordon A Awandare, Kirk A Rockett, Dominic Kwiatkowski

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

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  6. Polymorphism of Drug Resistance GenesTropical medicine and infectious disease · 2023
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  9. Evidence of a Recent Bottleneck inPathogens (Basel, Switzerland) · 2021
    Article
  10. Profiling antimalarial drug-resistant haplotypes inTherapeutic advances in infectious disease
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Lucas N Amenga-EtegoWest African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana. lamenga-etego@ug.edu.gh.ORCID http://orcid.org/0000-0003-4468-0506
Victor AsoalaNavrongo Health Research Centre, Ghana Health Service, P. O. Box 114, Navrongo, Ghana.
Godfred AgongoNavrongo Health Research Centre, Ghana Health Service, P. O. Box 114, Navrongo, Ghana.
Christopher JacobWellcome Centre for Human Genetics, University of Oxford, Headington, Oxford, OX3 7BN, UK.
Sonia GoncalvesWellcome Centre for Human Genetics, University of Oxford, Headington, Oxford, OX3 7BN, UK.
Gordon A AwandareWest African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana.
Kirk A RockettWellcome Centre for Human Genetics, University of Oxford, Headington, Oxford, OX3 7BN, UK.
Dominic KwiatkowskiWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.
Centre for Human Genetics · GBNavrongo Health Research Centre · GHUniversity of Ghana · GHWellcome Sanger Institute · GB

Funding

DELGEME Aspiring Leader 107740/z/15/zMedical Research Council G0600718Medical Research Council MR/M006212/1Medical Research Council and Department for International Development(DFID) G0600718Medical Research Council and Department for International Development(DFID) M006212Wellcome Trust 090770/Z/09/ZWellcome Trust 204911/Z/16/ZWellcome Trust 206194
6 · The paper itself

Abstract

backgroundAnti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana.

methodsA total of 4469 samples from uncomplicated malaria patients collected from 2009 to 2018 was submitted to the Wellcome Trust Sanger Institute, UK for DNA sequencing using MiSeq. Genotypes were successfully translated into haplotypes in 2694 and 846 mono infections respectively for pfdhfr and pfdhps genes and the combined pfhdfr/pfdhps genes across all years.

resultsAt the pfdhfr locus, a consistently high (> 60%) prevalence of parasites carrying triple mutants (IRNI) were detected from 2009 to 2018. Two double mutant haplotypes (NRNI and ICNI) were found, with haplotype NRNI having a much higher prevalence (average 13.8%) than ICNI (average 3.2%) across all years. Six pfdhps haplotypes were detected. Of these, prevalence of five fluctuated in a downward trend over time from 2009 to 2018, except a pfdhps double mutant (AGKAA), which increased consistently from 2.5% in 2009 to 78.2% in 2018. Across both genes, pfdhfr/pfdhps combined triple (NRNI + AAKAA) mutants were only detected in 2009, 2014, 2015 and 2018, prevalence of which fluctuated between 3.5 and 5.5%. The combined quadruple (IRNI + AAKAA) genotype increased in prevalence from 19.3% in 2009 to 87.5% in 2011 before fluctuating downwards to 19.6% in 2018 with an average prevalence of 37.4% within the nine years. Prevalence of parasites carrying the quintuple (IRNI + AGKAA or SGEAA) mutant haplotypes, which are highly refractory to SP increased over time from 14.0% in 2009 to 89.0% in 2016 before decreasing to 78.9 and 76.6% in 2017 and 2018 respectively. Though quintuple mutants are rising in prevalence in both malaria seasons, together these combined genotypes vary significantly within season but not between seasons.

conclusionsDespite high prevalence of pfdhfr triple mutants and combined pfdhfr/pfdhps quadruple and quintuple mutants in this setting SP may still be efficacious. These findings are significant as they highlight the need to continuously monitor SP resistance, particularly using deep targeted sequencing to ascertain changing resistance patterns.

Indexed as

Genetic VariationGenotypeAdolescentAntimalarialsChildChild, PreschoolDrug CombinationsDrug ResistanceFemaleGhanaHumansMalaria, FalciparumMalePlasmodium falciparumPyrimethamineSeasonsAntimalarialsDrug Combinationsfanasil, pyrimethamine drug combinationPyrimethamineSulfadoxineGenotypesHaplotypeMalariaPfdhfrPfdhpsSP resistanceTemporal

Identifiers

PMID33731134
PMCPMC7968364
OpenAlexW3137468834

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.